tbuckley/cabot-search huggingface dataset:
Temperature Control After In-Hospital Cardiac Arrest: A Randomized Clinical Trial
Authors: Sebastian Wolfrum, Kevin Roedl, Alexia Hanebutte, Rüdiger Pfeifer, Volkhard Kurowski, Reimer Riessen, Anne Daubmann, Stephan Braune, Gerold Söffker, Eric Bibiza-Freiwald, Karl Wegscheider, Heribert Schunkert, Holger Thiele, Stefan Kluge
Journal: Circulation (2022)

Background: This study was conducted to determine the effect of hypothermic temperature control after in-hospital cardiac arrest (IHCA) on mortality and functional outcome as compared with normothermia. Methods: An investigator initiated, open-label, blinded-outcome-assessor, multicenter, randomized controlled trial comparing hypothermic temperature control (32-34°C) for 24 h with normothermia after IHCA in 11 hospitals in Germany. The primary endpoint was all-cause mortality after 180 days. Secondary end points included in-hospital mortality and favorable functional outcome using the Cerebral Performance Category scale after 180 days. A Cerebral Performance Category score of 1 or 2 was defined as a favorable functional outcome. Results: A total of 1055 patients were screened for eligibility and 249 patients were randomized: 126 were assigned to hypothermic temperature control and 123 to normothermia. The mean age of the cohort was 72.6±10.4 years, 64% (152 of 236) were male, 73% (166 of 227) of cardiac arrests were witnessed, 25% (57 of 231) had an initial shockable rhythm, and time to return of spontaneous circulation was 16.4±10.5 minutes. Target temperature was reached within 4.2±2.8 hours after randomization in the hypothermic group and temperature was controlled for 48 hours at 37.0°±0.9°C in the normothermia group. Mortality by day 180 was 72.5% (87 of 120) in hypothermic temperature control arm, compared with 71.2% (84 of 118) in the normothermia group (relative risk, 1.03 [95% CI, 0.79–1.40]; P =0.822). In-hospital mortality was 62.5% (75 of 120) in the hypothermic temperature control as compared with 57.6% (68 of 118) in the normothermia group (relative risk, 1.11 [95% CI, 0.86–1.46, P =0.443). Favorable functional outcome (Cerebral Performance Category 1 or 2) by day 180 was 22.5% (27 of 120) in the hypothermic temperature control, compared with 23.7% (28 of 118) in the normothermia group (relative risk, 1.04 [95% CI, 0.78–1.44]; P =0.822). The study was prematurely terminated because of futility. Conclusions: Hypothermic temperature control as compared with normothermia did not improve survival nor functional outcome at day 180 in patients presenting with coma after IHCA. The HACA in-hospital trial (Hypothermia After Cardiac Arrest in-hospital) was underpowered and may have failed to detect clinically important differences between hypothermic temperature control and normothermia. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT00457431.
Correction to Open Access Status
Authors: Awinita Barpujari, Rohin Singh, David Hoyt
Journal: JAMA Surgery (2022)

Roberto Hernandez-Alejandro, MD; Luis I. Ruffolo, MD; Kazunari Sasaki, MD; Koji Tomiyama, MD, PhD; Mark S. Orloff, MD; Karen Pineda-Solis, MD; Amit Nair, MD; Jennie Errigo, BS; M. Katherine Dokus, MPH; Mark Cattral, MD; Ian D. McGilvray, MD, PhD; Anand Ghanekar, MD, PhD; Steven Gallinger, MD, MSc; Nazia Selzner, MD, PhD; Marco P. A. W. Claasen, MD; Ron Burkes, MD; Koji Hashimoto, MD, PhD; Masato Fujiki, MD; Cristiano Quintini, MD; Bassam N. Estfan, MD; Choon Hyuck David Kwon, MD, PhD; K. V. Narayanan Menon, MD; Federico Aucejo, MD; Gonzalo Sapisochin, MD, PhD, MSc
Is <i>Helicobacter pylori</i> infection inversely correlated with atopic, skin, and autoimmune diseases?
Authors: Taro Yasuma, Corina N. D’Alessandro‐Gabazza, Hajime Fujimoto, Tetsu Kobayashi, Ichiro Imoto, Esteban C. Gabazza
Journal: Allergy (2022)

All authors declared no conflict of interest regarding this letter.
The reversion of DNA methylation-induced miRNA silence via biomimetic nanoparticles-mediated gene delivery for efficient lung adenocarcinoma therapy
Authors: Lu Liang, Huiyu Cen, Jionghua Huang, Aiping Qin, Wenyan Xu, Siran Wang, Zhijun Chen, Lin Tan, Qiqi Zhang, Xiyong Yu, Xin Yang, Lingmin Zhang
Journal: Molecular Cancer (2022)

Lung cancer is one of the fatal cancers worldwide, and over 60% of patients are lung adenocarcinoma (LUAD). Our clinical data demonstrated that DNA methylation of the promoter region of miR-126-3p was upregulated, which led to the decreased expression of miR-126-3p in 67 cases of lung cancer tissues, implying that miR-126-3p acted as a tumor suppressor. Transduction of miR-126-3p is a potential therapeutic strategy for treating LUAD, yet the physiological environment and properties of miRNA challenge current transduction approaches.We evaluated the expression of miR-126-3p in 67 pairs of lung cancer tissues and the corresponding adjacent non-tumorous tissues by Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The relationship between the overall survival of lung cancer patients and miR-126-3p was analyzed by the Cancer Genome Atlas cohort database (Oncolnc, http://www.oncolnc.org ). We analyzed DNA methylation Methylation-specific PCR (MSP) analysis. To determine whether ADAM9 is the direct target of miR-126-3p, we performed the 3'-UTR luciferase reporter assay. The protein levels in the cells or tissues were evaluated with western blotting (WB) analysis. The biodistribution of nanoparticles were monitored by in vivo tracking system.We describe the development of novel stealth and matrix metalloproteinase 2 (MMP2)-activated biomimetic nanoparticles, which are constructed using MMP2-responsive peptides to bind the miR-126-3p (known as MAIN), and further camouflaged with red blood cell (RBC) membranes (hence named REMAIN). REMAIN was able to effectively transduce miRNA into lung cancer cells and release them via MMP2 responsiveness. Additionally, REMAIN possessed the advantages of the natural RBC membrane, including extended circulation time, lower toxicity, better biocompatibility, and immune escape. Moreover, in vitro and in vivo results demonstrated that REMAIN effectively induced apoptosis of lung cancer cells and inhibited LUAD development and progression by targeting ADAM9.The novel style of stealth and MMP2-activated biomimetic nanoparticles show great potential in miRNA delivery.
The WHO classification of haematolymphoid tumours: response to Swerdlow et al.
Authors: Ian A. Cree
Journal: Leukemia (2022)

I am grateful to the authors of this letter for their continued interest in this subject over many decades, and their past support for the WHO Classification of Tumours.Governance matters, and it was quite clear that the CAC mechanism did not meet our requirements and could not continue alongside the editorial board for the reasons given in my editorial [1].While the correspondents may find this disappointing, the new edition of the Haematolymphoid volume has been thoroughly reorganised and rewritten with the help of 420 authors and editors with multidisciplinary expertise and worldwide representation, including many members of the European Association for Haematopathology and the Society for Hematopathology, according to our published methodology [2, 3].The Haematolymphoid Tumours volume (5th ed.) is now published online in beta format [4] and readers can judge for themselves how we've done, with the opportunity for feedback from our website.Personally, I am very grateful to all involved who have worked tirelessly to achieve an excellent hierarchical classification as well as a level of detailed description of these disorders that have never been bettered.
Correction: Histone acetyltransferase PCAF Up-regulated cell apoptosis in hepatocellular carcinoma via acetylating histone H4 and inactivating AKT signaling
Authors: Xin Zheng, Xiaohong Gai, Feihu Ding, Zhongtang Lu, Kangsheng Tu, Yingmin Yao, Qingguang Liu
Journal: Molecular Cancer (2022)
John Launer: The art of paying attention
Authors: John Launer
Journal: BMJ (2022)

I'm not sure that I've ever been an exceptionally compassionate or empathetic doctor, and it would be for patients to say, rather than me.Possibly they'd have a range of views, depending on whether we got on well or my treatment made them better.Altogether, I'm a bit suspicious of training and publications that describe how to develop empathy and compassion (sometimes subtly implying saintliness in their authors), so in my own teaching I generally try to avoid tackling these topics head on.There are other qualities I prefer to focus on.Rita Charon, a New York physician and a pioneer in the field of narrative medicine, emphasises three qualities that she believes we should promote in medicine: attention, representation, and affiliation. 1She describes attention as "the most pivotal skill with which to endow a health professional who wants to be a healer."By representation she means the capacity to give a faithful and accurate account of a patient's words, images, thoughts, and utterances.Affiliation follows from these, when we bring our full selves into our practice.
Parents are urged to vaccinate 2-3 year olds against flu as NHS warns of “twindemic”
Authors: Elisabeth Mahase
Journal: BMJ (2022)

The UK Health Security Agency has urged parents to take up the offer to vaccinate their 2 and 3 year old children against flu this year, because of fears over a lack of natural immunity. The UKHSA said that most young children will not have encountered flu yet, owing to pandemic restrictions that have reduced the spread of the virus over the past two winters. It is also urging people in eligible clinical risk groups and pregnant women to get vaccinated (box 1). Box 1 ### Who is eligible for the flu vaccine?RETURN TO TEXT
High-throughput T cell receptor engineering by functional screening identifies candidates with enhanced potency and specificity
Authors: Rodrigo Vazquez-Lombardi, Johanna S. Jung, Fabrice S. Schlatter, Anna Mei, Natalia Rodrigues Mantuano, Florian Bieberich, Kai-Lin Hong, Jakub Kucharczyk, Edo Kapetanovic, Erik Aznauryan, Cédric R. Weber, Alfred Zippelius, Heinz Läubli, Sai T. Reddy
Journal: Immunity (2022)

A major challenge in adoptive T cell immunotherapy is the discovery of natural T cell receptors (TCRs) with high activity and specificity to tumor antigens. Engineering synthetic TCRs for increased tumor antigen recognition is complicated by the risk of introducing cross-reactivity and by the poor correlation that can exist between binding affinity and activity of TCRs in response to antigen (peptide-MHC). Here, we developed TCR-Engine, a method combining genome editing, computational design, and deep sequencing to engineer the functional activity and specificity of TCRs on the surface of a human T cell line at high throughput. We applied TCR-Engine to successfully engineer synthetic TCRs for increased potency and specificity to a clinically relevant tumor-associated antigen (MAGE-A3) and validated their translational potential through multiple in vitro and in vivo assessments of safety and efficacy. Thus, TCR-Engine represents a valuable technology for engineering of safe and potent synthetic TCRs for immunotherapy applications.
Myeloid cell interferon secretion restricts Zika flavivirus infection of developing and malignant human neural progenitor cells
Authors: Harry Bulstrode, Gemma C. Girdler, Tannia Gracia, Alexander Aivazidis, Ilias Moutsopoulos, Adam M.H. Young, John Hancock, Xiaoling He, Katherine Ridley, Zhaoyang Xu, John H. Stockley, John Finlay, Clement Hallou, Teodoro Fajardo, Daniel M. Fountain, Stijn van Dongen, Alexis Joannides, Robert Morris, Richard Mair, Colin Watts, Thomas Santarius, Stephen J. Price, Peter J.A. Hutchinson, Emma J. Hodson, Steven M. Pollard, Irina Mohorianu, Roger A. Barker, Trevor R. Sweeney, Omer Bayraktar, Fanni Gergely, David H. Rowitch
Journal: Neuron (2022)

Zika virus (ZIKV) can infect human developing brain (HDB) progenitors resulting in epidemic microcephaly, whereas analogous cellular tropism offers treatment potential for the adult brain cancer, glioblastoma (GBM). We compared productive ZIKV infection in HDB and GBM primary tissue explants that both contain SOX2+ neural progenitors. Strikingly, although the HDB proved uniformly vulnerable to ZIKV infection, GBM was more refractory, and this correlated with an innate immune expression signature. Indeed, GBM-derived CD11b+ microglia/macrophages were necessary and sufficient to protect progenitors against ZIKV infection in a non-cell autonomous manner. Using SOX2+ GBM cell lines, we found that CD11b+-conditioned medium containing type 1 interferon beta (IFNβ) promoted progenitor resistance to ZIKV, whereas inhibition of JAK1/2 signaling restored productive infection. Additionally, CD11b+ conditioned medium, and IFNβ treatment rendered HDB progenitor lines and explants refractory to ZIKV. These findings provide insight into neuroprotection for HDB progenitors as well as enhanced GBM oncolytic therapies.
Single-cell transcriptomics identifies pathogenic T-helper 17.1 cells and pro-inflammatory monocytes in immune checkpoint inhibitor-related pneumonitis
Authors: Amelie Franken, Pierre Van Mol, Sam Vanmassenhove, Elena Donders, Rogier Schepers, Thomas Van Brussel, Christophe Dooms, Jonas Yserbyt, Nico De Crem, Dries Testelmans, Walter De Wever, Kristiaan Nackaerts, Johan Vansteenkiste, Robin Vos, Stéphanie Humblet-Baron, Diether Lambrechts, Els Wauters
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Immune checkpoint inhibitor (ICI)-related pneumonitis is the most frequent fatal immune-related adverse event associated with programmed cell death protein-1/programmed death ligand-1 blockade. The pathophysiology however remains largely unknown, owing to limited and contradictory findings in existing literature pointing at either T-helper 1 or T-helper 17-mediated autoimmunity. In this study, we aimed to gain novel insights into the mechanisms of ICI-related pneumonitis, thereby identifying potential therapeutic targets. Methods In this prospective observational study, single-cell RNA and T-cell receptor sequencing was performed on bronchoalveolar lavage fluid of 11 patients with ICI-related pneumonitis and 6 demographically-matched patients with cancer without ICI-related pneumonitis. Single-cell transcriptomic immunophenotyping and cell fate mapping coupled to T-cell receptor repertoire analyses were performed. Results We observed enrichment of both CD4+ and CD8+ T cells in ICI-pneumonitis bronchoalveolar lavage fluid. The CD4+ T-cell compartment showed an increase of pathogenic T-helper 17.1 cells, characterized by high co-expression of TBX21 (encoding T-bet) and RORC (ROR-γ), IFN-G (IFN-γ), IL-17A , CSF2 (GM-CSF), and cytotoxicity genes. Type 1 regulatory T cells and naïve-like CD4+ T cells were also enriched. Within the CD8+ T-cell compartment, mainly effector memory T cells were increased. Correspondingly, myeloid cells in ICI-pneumonitis bronchoalveolar lavage fluid were relatively depleted of anti-inflammatory resident alveolar macrophages while pro-inflammatory ‘M1-like’ monocytes (expressing TNF , IL-1B , IL-6 , IL-23A, and GM-CSF receptor CSF2RA, CSF2RB ) were enriched compared with control samples. Importantly, a feedforward loop, in which GM-CSF production by pathogenic T-helper 17.1 cells promotes tissue inflammation and IL-23 production by pro-inflammatory monocytes and vice versa, has been well characterized in multiple autoimmune disorders but has never been identified in ICI-related pneumonitis. Conclusions Using single-cell transcriptomics, we identified accumulation of pathogenic T-helper 17.1 cells in ICI-pneumonitis bronchoalveolar lavage fluid—a phenotype explaining previous divergent findings on T-helper 1 versus T-helper 17 involvement in ICI-pneumonitis—,putatively engaging in detrimental crosstalk with pro-inflammatory ‘M1-like’ monocytes. This finding yields several novel potential therapeutic targets for the treatment of ICI-pneumonitis. Most notably repurposing anti-IL-23 merits further research as a potential efficacious and safe treatment for ICI-pneumonitis.
Combination of a novel heat shock protein 90-targeted photodynamic therapy with PD-1/PD-L1 blockade induces potent systemic antitumor efficacy and abscopal effect against breast cancers
Authors: Kensuke Kaneko, Chaitanya R Acharya, Hiroshi Nagata, Xiao Yang, Zachary Conrad Hartman, Amy Hobeika, Philip F Hughes, Timothy A J Haystead, Michael A Morse, Herbert Kim Lyerly, Takuya Osada
Journal: Journal for ImmunoTherapy of Cancer (2022)

We previously demonstrated potent antitumor activity against human breast cancer xenografts using photodynamic therapy (PDT) targeting a novel tumor-specific photosensitizer (HS201), which binds heat shock protein 90 (HS201-PDT). However, induction of systemic antitumor immunity by HS201-PDT alone or by the combination strategy with immune checkpoint blockade has yet to be determined. Using unilateral and bilateral implantation models of syngeneic breast tumors (E0771, MM3MG-HER2, and JC-HER3) in mice, we assessed whether HS201-PDT could induce local and systemic antitumor immunity. In an attempt to achieve a stronger abscopal effect for distant tumors, the combination strategy with anti-PD-L1 antibody was tested. Tumor-infiltrating leukocytes were analyzed by single cell RNA-sequencing and receptor-ligand interactome analysis to characterize in more detailed the mechanisms of action of the treatment and key signaling pathways involved. HS201-PDT demonstrated greater tumor control and survival in immune competent mice than in immunocompromised mice, suggesting the role of induced antitumor immunity; however, survival was modest and an abscopal effect on distant implanted tumor was weak. A combination of HS201-PDT with anti-PD-L1 antibody demonstrated the greatest antigen-specific immune response, tumor growth suppression, prolonged mouse survival time and abscopal effect. The most significant increase of intratumoral, activated CD8+T cells and decrease of exhausted CD8+T cells occurred following combination treatment compared with HS201-PDT monotherapy. Receptor-ligand interactome analysis showed marked enhancement of several pathways, such as CXCL, GALECTIN, GITRL, PECAM1 and NOTCH, associated with CD8+T cell activation in the combination group. Notably, the expression of the CXCR3 gene signature was the highest in the combination group, possibly explaining the enhanced tumor infiltration by T cells. The increased antitumor activity and upregulated CXCR3 gene signature induced by the combination of anti-PD-L1 antibody with HS201-PDT warrants the clinical testing of HS201-PDT combined with PD-1/PD-L1 blockade in patients with breast cancer, and the use of the CXCR3 gene signature as a biomarker.
Developmental dynamics of RNA translation in the human brain
Authors: Erin E. Duffy, Benjamin Finander, GiHun Choi, Ava C. Carter, Iva Pritisanac, Aqsa Alam, Victor Luria, Amir Karger, William Phu, Maxwell A. Sherman, Elena G. Assad, Naomi Pajarillo, Alexandra Khitun, Elizabeth E. Crouch, Sanika Ganesh, Jin Chen, Bonnie Berger, Nenad Sestan, Anne O’Donnell-Luria, Eric J. Huang, Eric C. Griffith, Julie D. Forman-Kay, Alan M. Moses, Brian T. Kalish, Michael E. Greenberg
Journal: Nature Neuroscience (2022)
The (un)learning of social functions and its significance for mental health
Authors: Aleya Flechsenhar, Philipp Kanske, Sören Krach, Christoph Korn, Katja Bertsch
Journal: Clinical Psychology Review (2022)

Social interactions are dynamic, context-dependent, and reciprocal events that influence prospective strategies and require constant practice and adaptation. This complexity of social interactions creates several research challenges. We propose a new framework encouraging future research to investigate not only individual differences in capacities relevant for social functioning and their underlying mechanisms, but also the flexibility to adapt or update one's social abilities. We suggest three key capacities relevant for social functioning: (1) social perception, (2) sharing emotions or empathizing, and (3) mentalizing. We elaborate on how adaptations in these capacities may be investigated on behavioral and neural levels. Research on these flexible adaptations of one's social behavior is needed to specify how humans actually "learn to be social". Learning to adapt implies plasticity of the relevant brain networks involved in the underlying social processes, indicating that social abilities are malleable for different contexts. To quantify such measures, researchers need to find ways to investigate learning through dynamic changes in adaptable social paradigms and examine several factors influencing social functioning within the three aformentioned social key capacities. This framework furthers insight concerning individual differences, provides a holistic approach to social functioning, and may improve interventions for ameliorating social abilities in patients.
Awake perception is associated with dedicated neuronal assemblies in the cerebral cortex
Authors: Anton Filipchuk, Joanna Schwenkgrub, Alain Destexhe, Brice Bathellier
Journal: Nature Neuroscience (2022)

Neural activity in the sensory cortex combines stimulus responses and ongoing activity, but it remains unclear whether these reflect the same underlying dynamics or separate processes. In the present study, we show in mice that, during wakefulness, the neuronal assemblies evoked by sounds in the auditory cortex and thalamus are specific to the stimulus and distinct from the assemblies observed in ongoing activity. By contrast, under three different anesthetics, evoked assemblies are indistinguishable from ongoing assemblies in the cortex. However, they remain distinct in the thalamus. A strong remapping of sensory responses accompanies this dynamic state change produced by anesthesia. Together, these results show that the awake cortex engages dedicated neuronal assemblies in response to sensory inputs, which we suggest is a network correlate of sensory perception.
The three-dimensional landscape of cortical chromatin accessibility in Alzheimer’s disease
Authors: Jaroslav Bendl, Mads E. Hauberg, Kiran Girdhar, Eunju Im, James M. Vicari, Samir Rahman, Michael B. Fernando, Kayla G. Townsley, Pengfei Dong, Ruth Misir, Steven P. Kleopoulos, Sarah M. Reach, Pasha Apontes, Biao Zeng, Wen Zhang, Georgios Voloudakis, Kristen J. Brennand, Ralph A. Nixon, Vahram Haroutunian, Gabriel E. Hoffman, John F. Fullard, Panos Roussos
Journal: Nature Neuroscience (2022)